Anti-SLC1A2 monoclonal antibody, clone 2E9

Background/objectiveRecently, a genome-wide association study showed a statistically significant association between the rs3794087 single nucleotide polymorphism (SNP) in the solute carrier family 1 - glial affinity glutamate transporter, member 2 (SLC1A2) and the risk for essential tremor (ET). However, four further association studies showed controversial results.We carried out a systematic review and a meta-analysis including all the studies published on the risk of ET related to this SNP.Materials and methodsThe systematic review was performed using several databases, the meta-analysis was carried out using the software Meta-DiSc 1.1.1, and heterogeneity between studies was tested using the Q statistic.ResultsThe meta-analysis included five association studies for the SLC1A2 rs3794087 SNP (1925 ET patients, 4914 controls) and the risk for ET. The global diagnostic odds ratio (95% confidence intervals) was 1.08 (0.79-1.48) for the total group. After excluding data from the discovery series (which was responsible for a high degree of heterogeneity), the global diagnostic odds ratio (95% confidence intervals) was 0.96 (0.74-1.23). The separate analysis in White and Asiatic individuals on the frequency of the minor allele of rs3794087 did not show significant differences between ET patients and controls in both subgroups after excluding the discovery series.ConclusionThe results of the meta-analysis suggest that rs3794087 is not associated with the risk for ET.

Fusion genes are chimeric genes formed in cancers through genomic aberrations such as translocations, amplifications, and rearrangements. To identify fusion genes in gastric cancer, we analyzed regions of chromosomal imbalance in a cohort of 106 primary gastric cancers and 27 cell lines derived from gastric cancers. Multiple samples exhibited genomic breakpoints in the 5' region of SLC1A2/EAAT2, a gene encoding a glutamate transporter. Analysis of a breakpoint-positive SNU16 cell line revealed expression of a CD44-SLC1A2 fusion transcript caused by a paracentric chromosomal inversion, which was predicted to produce a truncated but functional SLC1A2 protein. In primary tumors, CD44-SLC1A2 gene fusions were detected in 1 to 2% of gastric cancers, but not in adjacent matched normal gastric tissues. When we specifically silenced CD44-SLC1A2, cellular proliferation, invasion, and anchorage-independent growth were significantly reduced. Conversely, CD44-SLC1A2 overexpression in gastric cells stimulated these pro-oncogenic traits. CD44-SLC1A2 silencing caused significant reductions in intracellular glutamate concentrations and sensitized SNU16 cells to cisplatin, a commonly used chemotherapeutic agent in gastric cancer. We conclude that fusion of the SLC1A2 gene coding region to CD44 regulatory elements likely causes SLC1A2 transcriptional dysregulation, because tumors expressing high SLC1A2 levels also tended to be CD44-SLC1A2-positive. CD44-SLC1A2 may represent a class of gene fusions in cancers that establish a pro-oncogenic metabolic milieu favoring tumor growth and survival.